Cytosorbents Corporation

Good afternoon and welcome to the CITOSorbent fourth quarter and full year 2022 financial and operating results conference call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for questions. Please be advised that the call will be recorded at the company's request. At this time, I'd like to turn the call over to our moderator, Jody Hoover. Please go ahead, Mrs. Hoover.

Thank you and good afternoon. Welcome to the Cytosorbents Fourth Quarter and Full Year 2022 Financial and Operating Results Conference Call. Joining me today from the company are Dr. Philip Chan, Chief Executive Officer, Vincent Caponi, President and Chief Operating Officer, Kathleen Block, Chief Financial Officer, Dr. Eftimios Deliagiris, Chief Medical Officer, Dr. Christian Steiner, Executive Vice President of Sales and Marketing and Managing Director of Cytosorbents Europe GmbH. Christopher Kramer, Senior Vice President of Business Development. And Dr. Irina Kulinets, Senior Vice President of Global Regulatory. Before I turn the call over to Dr. Chan, I'd like to remind listeners that during the call, management's prepared remarks may contain forward-looking statements which are subject to risks and uncertainties. Management may make additional forward-looking statements in response to your questions today. Therefore, the company claims protection under safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Actual results may differ from results discussed today, and therefore, we refer you to a more detailed discussion of these risks and uncertainties in the company's filings with the SEC. Any projections as to the company's future performance represented by management include estimates today as of March 9, 2023, and we assume no obligation to update these projections in the future as market conditions change. During today's call, we will have an overview presentation covering the operating and financial highlights for the fourth quarter and full year 2022 by management. Following that presentation, we will open the line up to your questions during the live Q&A session with the rest of the management team. And now, it's my pleasure to turn the call over to Dr. Philip Chan.

Thank you very much, Jody, and good afternoon, everyone.

For the first slide, I'd like to just cover some recent operational highlights. First of all, we ended last year with more than 195,000 cumulative cytosine treatments delivered. as of the end of the year, up 20% from the end of 2021, and marking 10 years of cytosar commercialization. Second, our STAR-T pivotal trial passed the halfway point of enrollment with an acceleration of enrollment aided by addition of new Canadian sites following Health Canada approval of the study. We are on target to achieve 80 patients by spring of 2023 and complete enrollment of the study by the summer of 2023. We also added Dr. Richard Whitlock, professor of surgery at McMaster University Medical School and the Canadian research chair in cardiovascular surgery for the Population Health Research Institute, PHRI, as our Canadian principal investigator of the STAR-T trial, joining Dr. Michael Gibson and Dr. Michael Mack. He has an outstanding track record of trial execution and brings a superb network of Canadian clinical trial sites specializing in cardiovascular trials to the STAR-T trial. We also strengthened our cash balance with $5 million in non-diluted debt financing from Bridge Bank. And we also increased our product growth and our product gross margins recovered in the fourth quarter to 75% and are expected to reach 75 to 80 plus percent as we ramp volume manufacturing. Last but not least, our sales momentum from the fourth quarter of last year has extended into the first quarter of this year to date with expectation of sales growth in 2023. I've left most of the clinical update to Micah to cover later on in his slides. I now have the pleasure of welcoming Irina Kulinets to our management team. Dr. Irina Kulinets joins the senior management team as Senior Vice President of Global Regulatory. Her goals are to drive U.S. and Canada regulatory strategy and execution for drug-served ATR, as well as to oversee European Union MDR compliance. ARENA brings 30 years of experience in regulatory affairs and clinical research with a specialty in medical devices, having a track record of success leading to regulatory approval or clearance of many medical products via Class II 510K and Class III premarket approval or PMA pathways in the cardiovascular and neurovascular space. Most recently, ARENA served as Senior Vice President of Regulatory Affairs for Microvention, a division of the Terumo Corporation conglomerate that generated an estimated half a billion in annual sales last year. She has also worked for major companies such as Johnson & Johnson, Boston Scientific, Finisher, and others. And she also has extensive experience as a regulator and was appointed as a third-party FDA inspector and 510 reviewer on behalf of the FDA to review, assess, and approve new technologies. With that, I'd like to invite Irina

have a few words arena thank you feel for kind introduction and good afternoon everyone I am excited to be a part of site assortment team and with the current success of site assortment product on many markets and encouraging trends of clinical research I have high expectations for the patients and physician community using this product worldwide and and eagerly anticipate the success of site assortment products on the U.S. market. I'm looking forward to leading the registration of this lifesaving product in many important regions. This is a great opportunity to participate in the success of something so important.

Well, thanks so much, Irina. Thanks so much, Irina.

And now I'd like to turn it over to Kathy to discuss our financials. Kathy?

Thank you so much, Phil, and hello to everyone on the call today. I will be discussing fourth quarter and full year 2022 financial results, including revenues and gross margins. And then I'm going to also provide an update on our working capital and our cash runway. Next slide, please. Total revenues for the fourth quarter of 2022, which include both product sales and grant revenue, was approximately $9.4 million. a 13% decrease as compared to Q4 2021 total revenue of approximately $10.8 million. Q4 22 product sales were $7.6 million, a 21% decline over $9.7 million in Q4 2021 product sales. We note, however, that sales in Germany, our largest market, were $3.3 million in the fourth quarter of 2022, which is an increase of 33% over the prior Q3 2022 quarter. COVID-19 sales were negligible during the fourth quarter 22 as compared to $1.7 million in the fourth quarter of 2021. In addition, we experienced a decrease in the average exchange rate of the Euro to the US dollar, which lowered our fourth quarter 2022 product sales by approximately $865,000. Such that on a constant currency basis, fourth quarter 2022 core non-COVID product sales were actually $8.5 million, which represents a 6.4% increase from our $8 million in core non-COVID product sales a year ago. Our grant revenue for the 4th quarter was 1.7M dollars compared to 1.1M dollars in the prior year. And our gross profit margins on product sales were 75% for the 4th quarter 2022 compared to 78% for the prior year. And the decrease that we experienced was due primarily to inefficiencies related to the relocation of our manufacturing operations to our new facility, which occurred during 2022. Next slide please. This chart breaks out our core non-COVID-19 product sales and our COVID-19 product sales by quarter. And as you can see, except for the $300,000 in COVID-19 sales in the first quarter of 2022, COVID-19 product sales have declined to virtually zero for the remainder of the year. Fourth quarter, COVID-19 product sales were zero That compares to $1.7 million in COVID-19 product sales in the fourth quarter of the prior year. Note that Q4 2022 product sales are directionally higher than the immediately prior quarter, a quarter-over-quarter increase of 18%. And as I know Christian will be discussing later in the call, we are seeing positive trends in the market particularly in Germany, our largest market. Next slide, please. Total revenue for 2022, including both product sales and grant revenue, was $34.7 million compared to $43.2 million in 2021, a decrease of 21%. Product sales were $29.4 million, representing a decline of 27% over 2021 product sales of $40.1 million. COVID-19 sales were negligible, as we said, in 2022. That compares with 6.3 million in COVID sales for the prior year. The decrease in the average exchange rate of the Euro to US dollar lowered 2022 product sales by approximately $3.1 million, such that on a constant currency basis, 2022 core non-COVID product sales were $32.2 million, a 5% decrease compared to $33.8 million in core non-COVID-19 product sales one year ago. 2022 grant revenue was $5.3 million compared to 2021 grant revenue of $3.1 million. And product gross margins for the year were 70% in 2022 compared to 80% in 2021. This decrease is primarily due to the relocation, as I previously mentioned. We expect that as we increase production at our new facility during 2023, we will see gradual improvements in our gross margins. which should equal or exceed the 80% blended gross margins that we typically report it prior to 2022. Next slide please. This chart shows our annual product sales, and it's also broken down into COVID-19 product sales, the light blue part of the bar, and core non-COVID product sales, the darker blue part of the bar. And we note that on a constant currency basis, 2022 core product sales were 32.2 million, which is just 5% lower than core non-COVID-19 product sales of 33.8 million last year. We also like to point out on this chart that core non-COVID-19 product sales are 30% higher than they were in 2019, which is the year immediately prior to the start of the pandemic. Next slide, please. Lastly, I'd just like to say a few words about our working capital and cash runway. At December 31st, 22, we had $23.8 million in cash, which includes $1.7 million of restricted cash. This also includes $5 million of loan proceeds, which we received under our debt facility in December. This is an interest-only loan over the next 12 months and we are very comfortable with this level of debt at the moment. We are in discussions with Bridge Bank about extending our term loan commitment, which is scheduled to expire on March 24th, 2023. Based on our detailed 2023 operating budget, we believe we have available cash to fund our operations beyond the next 12 months. Conservation of cash is, of course, an important corporate priority. and we are focused on controlling expenses. We have and will continue to identify potential cost saving opportunities to reduce our cash burn. During 2022, we reduced our overall headcount by 10%. We shifted our R&D employees to solely grant funded programs. And in addition, we've reduced our inventory levels, providing for additional working capital. We have de minimis capital expenditures planned for 2023 compared to $6.1 million in actual capital expenditures in 2022. Our goal is through a combination of driving an increase in sales and gross margin along with cost-cutting measures to significantly reduce our cash burn and to further extend our operating runway. While the first quarter of 2023 is not yet complete, we are observing significant reductions in our quarterly cash burn. Our spend is laser-focused on and fully aligned with our strategic priorities, most notably our STAR-T clinical trial designed to support U.S. FDA marketing approval for drug Zorb ATR. And now that I've brought up clinical trials, it seems like the perfect time to turn the call over to our Chief Medical Officer, Dr. Athemius Deliagiris,

Please go ahead, Micah.

Thank you, Kathy.

And hello to everyone on the call today. For the next few minutes, we're going to discuss primarily the progress in the STAR-T trial, also provide an update on the remaining company clinical programs, and of course, highlight some major data releases that happened already this year. So next slide, please. So the headline for today's clinical update is that we have made solid progress and now have increased visibility as we're moving forward. The strategy that we discussed with you on the last earnings call of focusing all our resources, all our clinical resources on the STAR-T trial and expanding to Canada, I'm very happy to report that it's paying off. STAR-T is enrolling fast and has now crossed the halfway point with more than 50 patients enrolled. We can now reiterate the timelines previously stated that we will hit the next milestone of 80 patients this spring, and that the trial will fully enroll this summer. The STAR-D activities remain on pause, and the plan also remains to resume this study upon completion of STAR-T. Also very encouraging are the enrollment rates with the STAR-T registry. In fact, we have enough patients enrolled that we will have the initial data readouts before the first half of this year. We're also accelerating our trials in critical care, specifically our process randomized clinical study and our COSMOS international registry, which we will focus on this year to accelerate enrollment. And finally, the positive data flow for Cytosorb will continue in 2023. with a constant stream of presentations and publications in large international conference and peer-reviewed journals in all the therapeutic areas, including critical care, liver and kidney, and cardiac surgery. Next slide, please. Now, let's spend the next couple of slides talking about STAR-T. As I mentioned, we now have good visibility of the way forward. Just as a reminder, at the end of last year, in December, we received a green light from the DSMB who finished their first safety review after the first 40 patients were enrolled and recommended that we continue the study as planned without any modification. Since that time, we have experienced accelerating enrollment, and now the majority of sites participating in the trial are actively contributing. Canada came on quickly and came on fast, but has already contributed multiple patients in the study, and it's accelerating enrollment. Now that we are past the halfway point, we're working closely with our regulatory colleagues. And as a side note, I would like to also welcome and be very thankful for Irina joining us, such an experienced regulatory expert that will be critical in driving the filing to the FDA upon completion of the trial. And as we've shown you before, on the bottom of this slide, you see the table outlining the three milestones of the trial. with the first one that has already been completed, that we reviewed already. The second one, which is what you should be looking for next, happening in the spring, once we hit 80 patients enrolled. And then the final milestone, which represents the full enrollment of the study with 120 patients, the final analysis, and the DSMB closeout review, which we anticipate it will take place this summer.

Next slide, please.

I want to give you a little bit more insight in the next few months as the trial is coming to completion. So let's talk a little bit about what to expect in the near future for the STAR-T trial. First of all, we estimate that the trial will be fully enrolled by the time the previously scheduled interim analysis process would be completed, a process that requires a soft database log with full data cleaning and full event adjudications. I'd also like to remind you that performing an interim analysis comes with a statistical price, the so-called spend of alpha. Therefore, now, based on the FAST enrollment, we have an opportunity to preserve all the alpha for the final analysis by foregoing the interim analysis, and we plan to do so. I will emphasize that this positive development is a direct result of the FAST enrollment of the trial, which is directly related to the highly motivated investigative sites in the US and Canada. And it's not at all related to any safety or other known concerns. So what you should be looking for next is the enrollment of 80 patients, which similar as we did in late last year, will trigger a press release. And from that point on, they're following the second DSMB safety review. We anticipate that the interval between enrolling the ATF patients and executing the DSMB review will likely be similar to the one from the first review in approximately eight weeks.

Next slide.

Now for the next couple of minutes, I'd like to provide you with a brief update on the progress we're making on the remaining company clinical programs. First in line, let's talk about process. a randomized clinical study in patients with refractory shock that were executing in multiple sites in Germany. We now have the majority of those sites open and are in the process of executing an important protocol amendment that will allow earlier initiation of therapy and should also contribute to faster enrollment. This optimization of the trial was informed by observations from other studies, including our own CPC registry with its excellent results, but also from testimonials from real-world use that suggest that cytosol benefits are maximized with earlier initiation of therapy. This approach is also in line with our commercialization strategy of offering treatment now to patients before they develop organ failure and require organ support like continued renal replacement therapy with the use of a standalone hemoperfusion pump. We anticipate this amendment to be completed in the first half of the year and to drive faster enrollment proposals in 2023. Now let's turn our attention to the STAR Registry. I'm happy to report that enrollment in the registry is exceeding our own projections. We believe that this is in large part driven by the increasing adoption of ATR or antithrombotic removal as the standard of care in many European heart centers. We already have more than 200 patients enrolled, and 2023 is an exciting year since we're going to have the initial data readouts, starting with the presentation for the very large international conference of interventional cardiology, EuroPCR, in Paris this May. We also have submitted an additional analysis to the largest cardiovascular conference in the world, the European Society of Cardiology meeting that will take place in Amsterdam in August, and we also plan to present the European Association of Cardiothoracic Surgery in Vienna next October should our submissions be accepted, of course, to these meetings. Finally, let's talk about COSMOS. This year will be the year of COSMOS. We will focus our attention and increase our resources and prioritize progress in this important registry. We believe that this platform allows enrollment for all the remaining cytosol applications, with the exception of antithrombotic removal, across multiple therapeutic areas, and that the data from the COSMOS registry will generate a wealth of high-quality evidence, both on the clinical benefits, but also the value proposition of Sadosorb for the years to come. We're happy with the opening of the first few sites, the first two countries, Germany and Spain, and the first few sites, and are happy to see that enrollment has shown a slight uptick in the recent months. Just as a reminder, the CTC registry we have discussed previously in detail had the final results presented at the International European Society of Intensive Care Medicine meeting last year, and now the main results have been submitted for publication. So please be on the lookout for the formal paper to be released shortly. Next slide, please. During our last earnings call, we discussed about the flurry of new data in cardiac surgery that were presented at the European Association of Cardiothoracic Surgery. The study that really stood out was the multicenter analysis on staff endocarditis patients that was presented. I would like to spend a little more time now and refer you to the reference listed on the bottom for you to actually get the study online, find the study online since it has now been formally published. Staphylococcus aureus endocarditis is the most serious type of endocarditis. It carries the highest risk for morbidity, and it carries mortality rates that can approach 40%. In this multicenter study, a total of 130 patients with confirmed Staphylococcus aureus endocarditis underwent cardiac surgery and valve replacement. 75 of those patients were treated with Cytosorb, while 55 of those patients underwent surgery without Cytosorb. The main results are summarized on the slide. On the left-hand side, on the diagram, you see on the bottom left, the need for vasopressor support. These are drugs that are given intravenously and try to maintain blood pressure in the presence of hemodynamic instability. And patients who were treated with Cytosorb had reduced need for such agents throughout the early postoperative period, from right after surgery out to day three after the operation. What's more compelling is that the investigators specifically looked at three different mortality rates. First of all, patients who expired because of sepsis, and that was significantly lower among those treated with cytosol, 8 versus 22.8%. Then they look at 90-day mortality. That was 21.3% versus 40% in the control group. This represents a really significant absolute risk reduction of 18.7% in mortality. which in turn would translate to a number needed to treat to save the life of 5.3. The authors stated that they believed that these compelling benefits were in large part related to the fact of the ability of the cytosol device to remove not only cytokines, but also staphylococcal-specific toxins, such as staphylococcal hemolysin and toxic shock toxin.

Next slide.

And finally, the highlight recently that you have probably already seen in our recent press release is the fact that we are very happy to report that for the first time, our technology has been mentioned in practice guidelines. Specifically, the 2023 European Society of Anesthesiology and Intensive Care issued guidelines for the management of severe perioperative bleeding. And they have included intraoperative hemoabsorption in these guidelines, with a statement saying that it may be considered as an adjuvant therapy to reduce leading complications in patients on ticagrelor or rivaroxaban undergoing emergent cardiac or aortic surgery on CPB. Next slide, please. And you will probably hear a few more words about this major development and how it's gonna form a commercialization strategy from Christian coming up next. So, in conclusion, we now have visibility for STAR-T with more than half of the patients enrolled, and we're confident in the timelines of hitting the second milestone this spring and completing the trial enrollment this summer. We will proceed straight to final analysis with fully preserved alpha. There is no longer rationale for interim since the full enrollment will complete before the interim could be executed. We anticipate that we'll have top-line results from STAR-T by year's end, approximately three to four months after the last patient completes the study. STAR-D remains on hold, and the plan remains to restart right after we complete our operational responsibilities with STAR-T. STAR registry is ahead of schedule with antithrombotic removal now becoming increasingly standard of care in real-world practice. And finally, this year, we'll prioritize both process and COSMOS with the intent of speeding up enrollment and generating critical evidence in our critical care applications. I also would like to remind you that we have a fully staffed, very capable medical affairs team that the priority in Europe is to support our business in all of our therapeutic areas. We anticipate increasing adoption of our therapy in 2023 based on the feedback we get from ongoing interactions with KOLs and users who continue to express high enthusiasm about our therapy. Also, we believe that the constant stream of new and positive data presented at international conferences and the continuous flow of new positive publications across all of our therapeutic areas will be major tailwinds for our business and adoption of our therapy. So thank you for your attention.

And with this, I would like to turn it to Christian. Christian? Yeah, thank you, Marcus.

And good afternoon to everyone in the United States and good evening to Europe. Cathy and Phil have already described to you the overall situation and the status of our business development. The macroeconomic situation has not improved and remains to be challenging in many ways. I want to give you a few more insights about our commercialization outside the United States. and share with you what we are seeing in the markets. I do believe that we are already in the middle of the stabilization of our science of commercialization, although the environment in the markets characterized by shortage of personnel at the hospitals, inflation, energy costs, and so on, has not improved.

But again, we have improved. First slide, please.

In the first quarter 2022, we could further improve the number of customer visits in our direct markets. However, we are still significantly below the number we have achieved before the pandemic. For example, in Germany, it's still approximately 25% lower. The shortage of personnel on ICUs leaves little time for meetings with industry representatives and for educational events. However,

Over the last 12 months, we could continuously increase our face-to-face time with customers. This led to the beginning of the turnaround we have experienced in Q4 2022.

We could stop the decline of our business and increase the revenues by 16.9% compared to the quarter before. This is 15.3% higher than the comparable last quarter before the pandemic. in June 4, 2019. More customers are buying again. They are buying more frequently and placing average bigger orders. That shows us that the patient population is somehow normalizing and more treatments are conducted.

Next slide, please.

So much has been said already about the impact of the pandemic on the medical device business and about the challenging new situation in the healthcare systems. This chart is showing on an annual basis that although we have suffered from all these circumstances and needed to digest a 27% decline from the pandemic years, we nevertheless could close the first post-pandemic year 31% higher than the last pre-pandemic year. I believe that this is the last earning call we need to speak about the pandemic and its impacts. Although markets will not go back to their old situation, we from now on can concentrate on quarter-over-quarter and year-over-year growth.

Next slide, please.

These goals will partly be driven by several sales initiatives we have reported to you in the last year earnings calls. These are ongoing, and we will keep you updated regularly. But a very significant growth catalyst for the next quarters and years will be that we are now ready to start addressing new additional customer groups and entering the mainstream market in certain indications. The chart in the lower part of the slide is showing the early markets in green on the left and the big mainstream market on the right. Our growth so far was mainly coming from those early market customer groups. Some of our geographically markets like Germany, Austria, or Italy are now mature enough to start crossing the chasm towards mainstream customers. The possible application fields for side dissolve are so manifold that we have to focus on only a few indications which are most advanced, and these are the following. Number one, reversal of vasoplegic shock, which includes also the septic shock. Number two, intra- and postoperative use of Cytosol in infected endocarditis. And number three, antithrombotic drug removal in cardiac surgery patients. The first of those three indications is representing the biggest business opportunity, but also it's the most complex application with many co-founding factors influencing the therapy outcome. The second and the third indication are part of our cardiovascular therapeutic area and represent smaller business opportunities, but also promise a possibility to faster get standard of care status. I will give you some more insights about our activities in all three therapeutic areas, cardiovascular, critical care, and liver kidney with my next three slides.

Next slide, please.

The biggest news for our therapeutic area, cardiovascular, is that haemoabsorption therapy has made it into the new guidelines for the management of severe perioperative bleeding by the European Society of Anesthesiology and Intensive Care, which has been published on March 1st this year. Marcus has already reported to you about this major achievement, but I just wanted to add two facts which are very important to us from a commercialization point and investor point of view. The authors obviously avoid the product named Cytosorb, but only Cytosorb is specifically approved for the removal of ticagrenol and rivaroxaban, and this guideline entry is solely based on Cytosorb data and evidence. Furthermore, in this therapeutic area, several very relevant studies on Cytosorb therapy effects in infective endocarditis patients have recently been published or are submitted for publication. The body of evidence in the field is growing, and we can see the increasing excitement and momentum in the community. The attendance at congresses, symposia, and educational events is rising, and we also can say that the support from renowned KOLs is getting stronger.

Next slide, please.

In the therapeutic area of critical care, we also can report a significant step forward and the acceptance of our therapy by key opinion leaders. Although not yet in guidelines, the therapy has been integrated as a therapy option for certain patients in the consensus paper on sepsis-associated acute kidney injury by leading European nephrologists and intensivists published just a few days ago. Also of great potential impact, several publications on the impact of Salsorb on the underlying mechanisms of several diseases are either out or will be published within the next few weeks. These confirm and support the medical rationale of cellular therapy. In general, we see a new openness and a lot of excitement about our therapy in the intensive care community and with their KOLs. All the progress on the medical scientific side is feeding our marketing stories. and argumentation lines, and I'm sure we will see the impact of this development within the next few months and quarters.

Next slide, please.

Last but not least, I want to speak about our third and youngest therapeutic area, liver and kidney.

We have started two awareness campaigns on an international level, and we see a lot of interest arising in these two fields. One, Cytosol liver support in patients with liver dysfunction, and two, Cytosol protects the kidneys in rhabdomyolysis. There is no real solution for the medical needs in these two fields, and Cytosol has initially shown remarkable results. Inspired by those findings, there was recently an expert meeting on the topic rhabdomyolysis at the biggest German intensive care congress in Bremen, Germany. leading nephrologists and intensivists in this field have started to get to consensus on the use of sidelob in this application as well.

Next slide, please.

This slide should just illustrate for you how we are representing our company and the sidelob therapy at different medical conferences and trade shows. The two pictures in the lower part of the slide show that our symposia are attracting many, many attendees.

Next slide, please.

So to summarize, we had a very challenging year, 2022, with a declining business due to the turbulences in the healthcare markets caused by the pandemic. The macroeconomic circumstances have not yet improved and will remain challenging in 2023. However, 12 months of hard work have resulted in the turnaround we have seen in Q4 2022. And this stabilization has continued so far into one of this year.

And I'm very convinced that we just have started a new phase of growth for this company.

I hope I could give you some insights and a little flavor from the markets. And with this, I want to hand over to my colleague Vince Caponi our President and Chief Operating Officer. Thanks.

Thanks, Christian. As we prepare for commercialization in the U.S. and Canada, our core sales and marketing team has established a go-to-market launch plan, identifying key personnel and sales operations to facilitate rapid entry into the market. With a total addressable market of $250 million for Ticagler alone, We believe a blended sales model of direct and distributors will provide broad access to the market in a cost-effective manner. Our COVID-19 distributor experience in North America has aided us in identifying distributors in both Canada and the US that we can leverage to supplement our direct sales effort. We believe this blended sales approach will allow broader market access to the market and drive faster revenue growth in the early stages of launch with experienced distributors as part of the sales team. Regarding the antithrombotic removal application, we continue to receive positive feedback from our EU customers where we see ongoing adoption and growth in the market. A device capable of meeting this unmet medical need to reduce the risk of postoperative bleeding for patients that have undergone CPB has had positive feedback. Even among our U.S. clinical trial sites, we see enthusiasm for the development of a medical device for antithrombotic removal. If START-T trial is successful and based on our experience in Europe, we believe there is significant upside ahead of our intraoperative use of DrugSorb ATR during CPB and add-on applications related to hospital-wide use as a preoperative treatment and subject for future label expansions. Reimbursement is a key consideration when launching a new medical product. We believe, though, we believe DrugSorb ATR would likely fall under this TCET, or Transitional Coverage for Emerging Technologies, reimbursement program for breakthrough devices under CMS. A favorable program announcement from CMS, probably in late April, would strengthen the value proposition for DrugSorb ATR, especially in the elderly Medicare population. a major demographic we will address with DrugSorb ATR. However, given the value proposition we believe DrugSorb ATR presents, the TCET would be helpful, but not necessary for us to be successful in the market, in our opinion. In summary, as we finalize our commercial launch plans, our core commercial team is working closely with our clinical team to gain voice of the customer In addition, as we look to the commercialization, we are closely, we are working closely with our regulatory team, gating our build out of the commercial operations in line with our regulatory filing. Next slide, please. Regarding the new facility, the end of 2022 marked a significant milestone for the company with the successful transfer of polymer manufacturing to the new facility and complete integration of the company under one roof. The polymer plan is fully commissioned and producing polymer today, supplying our device manufacturing lines. An early look at KPIs suggests we should continue to see improvements in efficiency as a result of consolidating the operation under one roof and a contiguous manufacturing space and scale. We are currently ramping production to replace inventories that we utilize to bridge transfer of the operations and look forward to continued improvements in efficiency as we gain experience running the new plant. Moving now to cost of goods, the 2022 gross margins dipped to 70% driven by the two plant shutdowns associated with the transfer of operations and several other non-recurring items. We expect to see continuing increases in gross margin to historical levels of 80 plus percent as the year progresses in hand with increased sales as we experience recovery in our core business. Next slide, please. R&D and product development teams are focused in two key areas, HemaDefend BGA and DrugSorb ATR. The HEMA DEFEND market opportunity is large covering three market segments encompassing military, civilian, and plasma processing industries. Our initial entry into the market will be focused on military applications associated with the universal plasma, fresh whole blood, and freeze dried plasma applications. Follow on commercialization efforts will address the larger civilian market encompassing blood transfusions and the plasma processing industry. We continue to receive strong government funding for our research programs. In 2022, we received an additional $6.1 million in grant funding for our HemaDefend BGA product and Phase I grant for Cytosorb XL to address endotoxin removal. The backlog of grant funding is approximately $11.5 million currently, and it's important to note that the funding is non-dilutive, providing a cost-effective vehicle to advance the Cytosorb polymer platform. Product development continues to drive the DrugSorb technical manufacturing plan for finalizing packaging and validation of DrugSorb ATR in our new facility. This work in conjunction with our clinical trial data will support our future regulatory submission and the launch of DrugSorb ATR in the US and Canada. In conclusion, the R&D team remains focused on advancing these programs to support the development and monetization of these assets. Thank you. This now concludes my remarks. Let me turn it back to Phil.

Thank you very much, Vince.

So, our earnings release today covers much of this in greater detail, but just to give you some expectations for 2023. First of all, as you've heard today, we expect completion of the STAR-T pivotal trial in the U.S. and Canada this year with regulatory submission to FDA and Health Canada to follow. We have increased visibility on the likelihood now of drug-served HR contributing to future sales should the START-T trial be positive. We expect a rebound in international sales growth this year with economic relief for hospitals expected throughout Europe. And we have many new initiatives to drive sales growth, including new clinical data. We have, are now conducting full cytosine production from our new Princeton manufacturing facility with an expectation of a restoration of product gross margin to the 75 to 80 plus percent range that we have been able to achieve historically. And we also expect more normalized year-over-year comparisons now that we believe that the Euro has bottomed in 2022 and the fact that we did not have any COVID-related revenue or nominal COVID-related revenue in 2022, and as Christian mentioned, We will not need to make these core versus non-core comparisons this year. Last but not least, we expect to have reduced cash burn with tight control over expenses with no major capital expenditures with our current cash balance expected to be more than sufficient to drive our 2023 operating plan. With that, that concludes our current prepared remarks. Operator, please open the call up. for the Q&A session.

Thank you. As a reminder, if you do have a question, please press star 1 on your touch-tone phone. Please make sure your mute button is turned off to allow your SINO to reach our equipment. Questions now come in from the analysts with management responding. Please hold while we pull for questions. Our first question comes from Mike Sarcone with Jefferies. Please go ahead.

Hey, good afternoon, and thanks for taking my questions. Hi, Mike. So my first one, just, you know, as it relates to STAR-T, can you maybe talk to us about how you're thinking about approval timelines post-submission and top-line data presentation?

Yeah, thank you. Thanks, Mike. Laikas and Irina, would you like to comment on that? Sure.

Thank you, Cyril. I can comment on that. At the moment, we are developing our regulatory strategy and would be able to inform the investment community when the regulatory strategy would be finalized. We are still waiting for results of clinical studies. and will be acting exactly upon receiving the favorable results.

Okay, thank you. And just my second question, you talked about a continued focus on reducing OPEX, and you've made some progress so far. Can you just elaborate? Are there any areas for incremental improvement that you could streamline even further?

Kathy, did you want to take that?

Sure, Phil, I can take that. You know, we're constantly looking at making sure that we're focused on our core initiatives. And, you know, you do this in waves, right? You do one pass and then another pass and then another pass. One of the things that we did, as Mike has talked about earlier, was we paused our STAR-D trial. So, we can, we saved an estimated 4Million dollars in costs in 2023 by just putting that trial on pause. So we're always looking for opportunities where, as we review our budget versus actual, where we have non essential things. I can tell you that not having capital expenditures this year will save us 6.1Million dollars, but we're open to other opportunities as we review our operating and our budget versus actual comparisons. I think you'll see dramatic reductions in the burn this year, really dramatic.

Okay, great. Thank you. Thanks, Mike.

Our next question comes from Josh Jennings with DD Cohen. Please go ahead.

Hi. Good afternoon. Thanks for taking the questions. Phil, it was great to see you earlier this week. Congratulations again on the guideline announcement. I was hoping to just ask first on the guidelines. I think there's going to be some star registry readouts as well throughout this year. How should we be thinking about, I guess, the commercial adoption ramp for drugs or ATR in maybe the second half of 2023 or maybe throughout 2023? Are these big catalysts or is the STAR-T trial really going to be the big driver of adoption, not only approval adoption in the United States, but also the big driver adoption internationally.

Thanks, Josh. Micah, did you want to take that question?

Sure. Let me just, you know, first of all, the guidelines you heard from multiple people on the call today, we see that as a major development. Getting into guidelines is really a milestone for any intervention, any therapy, any drug, any device. So we think that's definitely a tailwind. It gives a different stature to the therapy. And of course, it gives the credibility from the review of tens of experts who formed this guideline committee. So there's no question. I think that's a positive. The Star Registry will have serial data readouts. We're hoping this year. As I mentioned, one presentation is already locked in this May in Paris in a massive meeting, the EUPCR meeting. But we think we're going to have more. And the reason I'm going to have sequential analysis is because we're seeing this robust enrollment. The numbers keep going up, and therefore, as statistical power increases, we're able to look at subgroups, different drugs, different types of patients, different types of surgery. So we think the body of evidence will continue to grow and will support, you know, what we're already seeing, which is an increasing adoption and increasingly as a standard of care in many heart centers. The STAR-T trial will open up the U.S., the North American market, U.S. and Canada, hopefully, if positive, of course. And once that's in play, we think then the story around ATR will be complete, in addition with some health economic analysis that I've already begun making their way from different health care systems, showing that there's a lot of cost savings associated with that procedure. So I hope that helps.

Definitely. Thanks for that, gentlemen. wanted to ask about the gross margin expansion and the return to that 75% to 80% range on product gross margins. Is there any way to break out just the reliance on that expansion to volume growth versus some of the cost reduction issues or recovery in costs? And also, just on top of that, is any pricing dynamics for Cytosorb that we should understand?

Vince, do you want to take the first part of that or Kathy?

Sure.

And then Christian, maybe you can talk about the pricing stability. Thanks.

Okay. Sure. I'll take the first part about the gross margin. I mean, there will be efficiencies associated with this new facility and actually just the reduction in cost just out of efficiencies because we're under one roof as opposed to two sites we were in previously. But the second thing is the volume in the business is starting to come back and The fact that we've scaled so much now, you know, the overhead absorption will be much better as we drive more volume out of here. So, you know, continued gross margin reduction will be a factor of both, obviously, improvements in efficiency because of the new location, but also increases demand from the market, and that will continue to drive the price. And obviously, as most businesses that are volume-driven such as this, you know, the higher the volume, it drops relatively quickly. with increasing volume.

Christian? Thank you, Josh, for the question.

I have to say the price stability for Cysozorp is very high. So we have very stable end customer prices and even, could slightly increase prices in different markets. So this is mainly backed up by a continuous expansion of the value of the therapy. So as you have heard from Michael, there's a continuous stream of new clinical data, which really is supporting the price and supporting the value proposition. And I think we are not yet finished with this development. and can show in the next two quarters and years an increased body of evidence and much more support for the therapy. So very stable pricing, I'd say, all over the world.

Great. Thanks. Maybe just one last question. Phil, it's a little bit just here, sometimes hard for us to track some of these international markets, but how is the competitive landscape for hemopurification technology shaping up? Anything we should have on our radar? Thanks so much.

Yeah, Josh, thanks for the questions. You know, I think that from a competitive standpoint, you can look at the level of competitiveness of our technology based on others just by looking at the volume of publications that have been put out by users over the years. You know, we have some Chinese competitors that are trying to break into the acute care marketplace, but if you do a search on their technology or if you do a search on really probably our major competitor, which is Baxter and their offerings, you can see that the volume of those publications are very low, considering the amount of time they've been in the marketplace, compared to our publication list, which continues to grow significantly every single year to, again, hundreds and hundreds of published articles now. So I think that we are continuing to remain the leader in the blood purification space to treat life-threatening inflammation and acute care diseases. We are the leader. In fact, the only player approved specifically to reduce antithrombotic agents in the European Union under our CE-MARCS certificate and continue to drive that leadership through new innovation and some of the studies that you've seen in Staph aureus endocarditis in acute respiratory distress syndrome and in liver treatment of acute liver disease and many others.

Excellent. Thanks, Phil. Great. Thanks, Josh.

The next question comes from Sean Lee with HC Wainwright. Please go ahead.

Good afternoon, guys, and thanks for taking my questions. My first question is, previously you mentioned that the revenue reduction in 2022 was mostly due to several headwinds, including the prevalence of mild COVID cases that limited access to hospitals. So I was wondering, have those headwinds cleared up so far this year, and what's your outlook for 2023?

Yeah, thanks, Sean. Maybe, Christian, you can comment on that, and if I can comment as well.

Thank you very much for the question. I think the situation is very complex, including the pandemic and after the pandemic. Why we have in the beginning of the pandemic had a lot of treatments of COVID patients and our sales and revenues was surging. When vaccination became available for the disease and also the virus has changed, then we had much easier cases and not so many ICU patients from COVID. And so we had to treat less COVID patients. On the other hand, during this pandemic, there was a lot of impact on the healthcare systems. So in the beginning, a lot of ICUs were just blocked for COVID patients, so that other patients could not even enter the ICU. Because of this, a lot of surgeries have been postponed or even canceled. And this has led to a lot of deaths of patients because they could not be operated or treated. So this together with the COVID pandemic and the death of many people who died from this disease or this viral disease, a big proportion of the elderly population has died or suffered. And this has also led to the situation that in 2022, we had less patients on the ICUs. while the situation with the limited personnel in ICU is remaining, I think patients are slowly coming back. And this is mainly because the surgery programs have been accelerated again and not yet in full speed, but much better than in the beginning of 2022. And yeah, I think this is mainly describing the situation with the patients.

Yeah, you know, I think, as Christian mentioned, the further we – I think the FDA will actually call an end to the pandemic soon, given that the rates of COVID are very low around the world. And I think that the impact that COVID will have on our markets will sequentially decline. Certainly, a number of the issues that we face in the market today in terms of staffing shortages that are seen worldwide, particularly in nursing, remain. But I think gradually those things will get better. One of the major things that I mentioned in my remarks that really hurt was the drop in the euro and the weakness in the euro, given that a lot of our – the majority of in fact, of our revenue, our base in euro, that drop in the euro caused a significant drop in our revenue base in dollars. And so I think that given that the euro has likely bottomed as of last year, it's still close to parity to the US dollar, but I think that predictions are that the euro will remain stronger than the dollar, and so year-over-year comparisons should look better. So I think that's one thing that we look forward to not having to talk about every quarter. But I think other things are improving as well, but certainly it's been helpful that our stock price has improved, which opens up a lot of opportunities for us to gain new investors and other things. So thank you.

Great. Thank you. My second question is on the endocarditis study. The results are certainly very encouraging. So I was wondering whether a similarly designed study, a prospective study, could be used to support U.S. approval in that indication.

Micah, do you want to take that question? Sure.

So, yeah, endocarditis, it's an exciting area. You know, last year we hired our vice president of medical cardiovascular, Dr. Daniel Wendt, who was a distinguished cardiac surgeon for many years and kept telling us about the clear benefits that he saw and how well his patients were doing when treated with cytoscopy of his endocarditis patients. And now we're seeing, you know, again, data coming out from multiple centers suggesting that that managing hyperinflammation, controlling hemodynamics, very important in the outcomes of these patients. So absolutely, there's a possibility for us to design a prospective and execute a prospective study. However, what you heard from the last earnings, and you're also hearing again today from us, is that there's also a need and desire to stay focused and to execute at a task at hand. So with STAR-T and STAR-D already determined as being our next two studies, I think an endocarditis study would fit very nicely down the road since we would be working with the same institutions, the same physicians, the same investigators. And with the data accumulating, we could probably identify the right population study. So focus on antithrombotic removal for the near term, but certainly looking at endocarditis as an opportunity in the midterm.

I appreciate your thoughts. Thanks. That's all I have. Thanks, Sean.

Next question comes from Tom Kerr with Zacks Investment Research. Please go ahead.

Hi, guys. Most of my questions have been asked and answered. Just two quick financial ones. Can you refresh my memory on the grant income backlog? Is that received over one year? Does that get spread out over two to three years? I forget.

Yeah, the grant backlog is $11.5 million, and it's typically spread out over multiple years. These contracts with the DOD and other agencies are typically multi-year contracts where those dollars are earned over the course of the contract.

Okay, but we don't know if this is a two- or three-year contract or related to timeframe?

It's a compilation of many different grants, in fact, and so many of those grants, particularly the ones we received last year, or those contracts, still have a two- to three-year timeframe on them. But it varies. Some are near completion, but some are just beginning.

Got it. Okay. And then just last question is on the capital expenditures. I understand it's going to be diminished this year. But does that have to get ramped back up over the next three to five years? Will it ever get back in the millions? Or can you operate this business at very, very low CapEx needs?

Kathy, did you want to talk about that and maybe touch on the commercial expansion as well? Yes. If drugs are of ATR, that's approved.

Yeah, I think that, you know, with regard to our capex of 6Million last year, that was because of the opening of our new manufacturing facility. So, so that was a, that was a big bolus of expense that we won't be experiencing hopefully for another 10 years. But our capacity has has grown 4fold, you know, from 80Million to now. 350 to 400Million in annual capacity. So we should be pretty well set at our current plant prior to. Opening up the new plant, our capex spend was generally. 300 to 500,000 dollars a year and now we have all new equipment in our facility. We have new labs and so we can expect that maintenance capital needs to be low. as we move forward, I would say over the next five years at a minimum.

Okay. All right. That's all I have. Thank you. Thanks, Tom.

And at this time, I would like to turn the call back to management for any additional or closing remarks.

Well, thank you very much, everyone, for taking the time get on this call with us and get an update on Cytosorbents progress. We're very excited about the near-term future, particularly with the pending completion of the STAR-T pivotal trial. If you have any questions that were not answered today, please feel free to reach out to Kathy at kblock, K-B-L-O-C-H, at cytosorbents.com, and we'll try to get you those answers as soon as we can. Thank you, everyone, and have a good night.

Thank you. That concludes our conference for today. I'd like to thank everyone for their participation and have a great day.